The worldwide problem of hepatitis B virus infection and its association with chronic liver disease and hepatocellular carcinoma have necessitated the development of a safe and effective vaccine. Both the currently licensed vaccines are beyond the financial reaches of the health care programs of countries where there is an urgent need for mass vaccination. Furthermore, some individuals on being vaccinated fail to make an antibody response. It is likely that this group on non-responders to the vaccine might be akin to individuals who are unable to mount an immune response on exposure to HBV, became chronic carriers. The question that is being addressed is, can an alternative vaccine overcome this nonresponsiveness? The overall aim of the research is to evaluate the utility of monoclonal anti-idiotypic antibodies which the investigators have already made and fully characterized, and is known to mimic the group specific a determinant of HBsAg to overcome some of the limitations of the two licensed vaccines. The studies proposed to be undertaken (using both mouse lymph node cells and human peripheral blood lymphocytes) will allow the investigators to compare in vitro responsiveness to antigen versus monoclonal anti-id. An important issue will be the ability of anti-id to elicit a response in lymphocytes obtained both from human subjects who in vivo have not responded to infection with hepatitis B virus (i.e., are carriers) and non-responders to the licensed hepatitis vaccine. The experiments described under Specific Aim II will permit an examination of whether anti-id derived peptides either alone or in combination with peptide sequences from HBs Ag itself could contribute to the rational design of a new vaccine for hepatitis B. These workers are also interested in investigating the possibility that T suppressor activity may be the mechanistic basis for the development of the carrier status in this infection and the non-responsiveness of some vaccines. Finally, the results obtained from purified subsets of peripheral blood lymphocytes will be reinforced by making appropriate T cell lines and clones and characterizing their response upon stimulation by antigen or its surrogate in the form of anti-id. Since the investigators have already made the monoclonal anti-ids and have promising results from preliminary in vitro T cell proliferation assays using our anti-ids, it is believed that the submitted project is a feasible one and well within the investigators' expertise.